Life Sciences 2013-02-07

An alpha1-adrenoceptor blocker terazosin improves urine storage function in the spinal cord in spinal cord injured rats.

Minoru Miyazato, Takuma Oshiro, Michael B Chancellor, William C de Groat, Naoki Yoshimura, Seiichi Saito

Index: Life Sci. 92(2) , 125-30, (2013)

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Abstract

To confirm the role of alpha1-adrenoceptor (α(1)-AR) in the spinal cord, we investigated the effect of intrathecal application of terazosin, a non-selective α(1)-AR blocker, on the micturition reflex, as well as the change of α(1)-AR subtypes mRNA in the lumbosacral spinal cord using spinal cord injury (SCI) rats.Adult female Sprague-Dawley rats were used 4 weeks after Th9-10 spinal cord transection. 1) Continuous cystometry was performed under an awake condition to examine the effect of intrathecal terazosin, a non-selective α(1)-AR blocker, at the level of L6-S1 spinal cord. 2) We also investigated the effect of intravenous phenylephrine, an α1-AR agonist, with or without intrathecal terazosin. 3) Quantification of α(1)-AR subtype mRNA in the L6-S1 lumbosacral spinal cord was performed in normal and SCI rats.1) Terazosin (0.01-10 μg) inhibited the number of non-voiding bladder contractions, and increased bladder capacity by 73%. 2) Phenylephrine (0.1 mg/kg) reduced bladder capacity by 17%, and voiding efficiency by 20%. Intrathecal terazosin blocked the effect of intravenous phenylephrine. 3) α(1)-AR subtype mRNA levels was all increased after SCI.These results suggest that α(1)-AR facilitates the micturition reflex in the spinal cord, and α(1)-AR blockers applied in the lumbosacral spinal inhibits this effect. Upregulation of α(1)-AR in the lumbosacral spinal cord could be involved in the genesis of detrusor overactivity after SCI. Therefore, if α(1)-AR blockers pass the blood-brain barrier, they could act in the spinal cord to improve storage function in patients with detrusor overactivity (DO).Copyright © 2012 Elsevier Inc. All rights reserved.